Department of Medicine Milestones

Faculty in the Department of Medicine have been performing basic research translated into clinical medicine for more than 80 years. We have a long tradition of working on important problems that advance clinical care. Below is a small sample of that body of work selected by the Department's Executive Committee.

2000-Present

Year

Milestone

2014

Wei Zeng , Ben Zhang and colleagues carried out a large scale study of East Asians which identified six new loci associated with colorectal cancer risk.

2014

Ning Wei, Rupesh Chaturvedi, Keith T. Wilson, and collaborators found that peroxisome proliferator-activated receptor δ promoted colonic inflammation and tumor growth.

2014

Jin Chen, Shan Wang , Dana M. Brantley-Sieders and colleagues revealed that genetic and pharmacologic inhibition of EPHA2 promotes apoptosis in NSCLC.

2014

Robert J. Coffey, Cunxi Li, Yang Wang, Zheng Cao, Ramona Graves-Deal, Anne Powell and collaborators uncovered how excess PLAC8 promotes an unconventional ERK2-dependent EMT in colon cancer.

2014

David M. Aronoff and colleagues discovered that Prostaglandin E₂ suppresses allergic sensitization and lung inflammation by targeting the E prostanoid 2 receptor on T cells.

2014

Billy Hudson, Julie Hudson, Aaron Fidler, Roberto Vanacore, Sergei Chetyrkin, Vadim Pedchenko, Gautam Bhave, Dorin-Bogdan Borza and other researchers in the Aspirnauts Inititiative discovered that a unique covalent bond in basement membrane is a primordial innovation for tissue evolution.

2013

Dorin-Bogdan Boraza’s research group uncovered how the neonatal Fc Receptor Promotes Immune Complex-Mediated Glomerular Disease.

2013

Wes Ely, Pratik P. Pandharipande, Robert S. Dittus. Gordon R. Bernard, Eduard E. Vasilevskis, Nathan E. Brummel, James C. Jackson, Timothy D. Girard other other BRAIN ICU investigators revealed how survivors of long-term illness often suffer from a disabling prolonged form of cognitive impairment.

2013

William Pao, Monica Red Brewer, Lai Darson and collaborators reported the mechanism for activation of mutated epidermal growth factor receptors in lung cancer.

2013

Mark Boothby , James W. Thomas and colleagues defined the requirement for Rictor in homeostasis and function of mature B lymphoid cells.

2013

Carlos Arteaga , Ariella Hanker, Justin M. Balko, Christian D. Young, Violetta Sanchez, Cammie R. Sutton, and collaborators discovered how mutations in PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies.

2013

Robert J. Coffey’s group elucidated the transformation of polarized epithelial cells by apical mistrafficking of epiregulin.

2013

Richard M. Peek Jr., Jennifer M. Noto, Jennifer Gaddy, Blanca Piazuelo, Judith Romero-Gallo, Giovanni Suarez, John Loh, Douglas Morgan, Keith Wilson, Pelayo Correa, Timothy Cover, and colleagues illuminated how iron deficiency accelerates Helicobacter pylori-induced carcinogenesis in rodents and humans.

2012

April Pettit and colleagues described the index case of fungal meningitis related to injection with contaminated steroids and triggered a public health response to prevent additional cases and deaths.

2012

Rick Peek and colleagues demonstrate that iron deficiency accelerates H. pylori-induced carcinogenesis.

2012

Ray Harris’s group identifies a critical role for CSF-1 signaling in recovery from acute kidney injury.

2012

Volker Haase shows that hypoxia-inducible factor regulates hepcidin via erythropoietin-induced erythropoiesis.

2012

William Pao and others identify BRAF gene mutations in some lung cancers with acquired resistance to EFR inhibitors.

2012

Sunil Kripalani and the Pharmacist Intervention for Low Literacy in Cardiovascular Disease Study Group find no beneficial effect of a pharmacist intervention on clinically important medication errors.

2012

Justin Balko , Carlos Arteaga, and others identify deficiency of dual specificity protein phosphatase 4 (DUSP4), an ERK phosphatase, as a mechanism of drug resistance in breast cancer.

2012

Takamune Takahashi’s group finds that thrombospondin-1 acts as a ligand for CD148 tyrosine phosphatase.

2012

Chris Williams reports that blood vessel epicardial substance prevents epithelial-mesenchymal transition, a critical step in the progression of epithelial colorectal carcinomas.

2012

Jeff Sosman, with Igor Puzanov, leads landmark trial studying the effect of vemurafenib on survival in BRAF V600-mutant advanced melanoma.

2011

William Pao and Mia Levy launch MyCancerGenome, the first internet-based decision support tool to help physicians and researchers track the latest developments in personalized cancer medicine and connect with clinical research trials for their patients.

2011

Harvey J. Murff, Theodore Speroff, and colleagues develop new methods using natural language processing to detect adverse events after surgery using an electronic medical record.

2011

Robert Miller, John Newman, and James Sheller identify bronchiolitis obliterans in men during military service in Iraq and Afghanistan.

2010

Josh Denney, Dan Roden and others demonstrate the feasibility of using a phenome-wide scan to discover gene-disease associations.

2010

Billy Hudson, Vadim Pedchenko, and others describe the molecular mechanism of Goodpasture's disease, in which conformational change in the alpha3NC1 and alpha5NC1 domain subunits of type IV collagen in the glomerular basement membrane elicits an autoimmune response.

2010

Tim Sterling and colleagues report results of an international clinical trial that supports a new, shorter, and more effective chemotherapeutic regimen for treatment of latent tuberculosis.

2010

Olivier Boutaud, John Oates, Jack Roberts and others report that Acetaminophen inhibits hemoprotein-catalyzed lipid peroxidation and attenuates rhabdomyolysis-induced renal failure.

2010

Dan Roden, Dawood Darbar and others identify genetic variants contributing to cardiac arrhythmias.

2009

Kathy Murray and Mike Stein, together with Wayne Ray, report the effect of antipsychotic medications on the risk of sudden death.

2009

Richard D'Aquila and colleagues indicate that the APOBEC3 defense system in lymphocytes can partially defend against HIV-1 at physiological levels of expression, even if HIV-1 expresses a countermeasure, highlighting the potential of attempting to increase expression of these defensive proteins.

2009

Keipp Talbot and colleagues report how immunization of school age children against influenza impacts older adults.

2009

Alfred George identified a genetic modifier of congenital long-QT syndrome.

2008

John Oates and Clinical Pharmacology fellow David Adler describe a patient with inherited phospholipase C2 deficiency characterized by impaired eicosanoid biosynthesis, small intestinal ulceration and platelet dysfunction.

2008

Mike Stein, Dan Roden and Ute Schwartz identify genetic determinants of the initial response to warfarin.

2008

Spryos Kalams, David Haas, and colleagues identify HIV-specific CD8+ T cells in CSF of HIV-infected subjects.

2008

Tom Talbot plays a prominent national leadership role to increase immunization of health care workers against influenza.

2008

Pingsheng Wu, Tina Hartert and colleagues demonstrate winter virus seasonality as a causal factor in asthma development.

2008

Alfred George discovered the functional basis for familial migraine associated with brain sodium channel mutations.

2007

Tim Sterling, ChristinaFiske and colleagues identify risk factors and immunogenetic predictors of extrapulmonary tuberculosis.

2007

Tim Sterling, Vlada Melekhin, and colleagues find that pregnancy slows HIV-1 immunodeficiency progression during antiretroviral therapy.

2007

Wonder Drake and colleagues demonstrate immune responses to specific mycobacterial antigens in sarcoidosis, strengthening support for a pathogenetic role identified by their earlier findings of an association of mycobacterial nucleic acids with sarcoidosis.

2007

Jeffrey Smith defined single nucleotide polymorphisms spanning the entire zebrafish genome.

2007

Alfred George elucidated functional consequences of heart sodium channel mutations that predispose to sudden infant death syndrome

2007

Tim Blackwell and colleagues report that NF-κB pathway signaling is important for lung cancer development

2007

James Loyd and colleagues discovered that telomerase mutations cause disease in some families with idiopathic pulmonary fibrosis

2006

Bjorn Knollmann and others in the division identify a role for Casq2 deficiency in catecholamine-induced polymorphic ventricular tachycardia.

2006

David Haas and colleagues identify genomic predictors of response to, and toxicity of, antiretroviral drugs.

2006

Ela Knapik identified the gene encoding a secretory vesicle coat protein as essential for craniofacial development.

2006

Gordon Bernard, Art Wheeler and the ARDS network investigators report that a conservative strategy of fluid management reduces the duration of mechanical ventilation and intensive care without increasing nonpulmonary-organ failures in patients with Acute Lung Injury.

2005

Dan Roden and colleagues identify genetic factors that predispose to drug-induced cardiac arrhythmia.

2005

Todd Hulgan, Tim Sterling, Bryan Shepherd and colleagues are the first to identify that the percentage of CD4+ T lymphocytes independently adds to the absolute count for clinical prediction HIV disease progression during antiretroviral therapy.

2005

Tim Cover and colleagues define multi-functional effects of a Helicobacter pylori toxin, VacA.

2005

Guanqing Wu discovered the functional importance of the recessive polycystic kidney disease gene in morphogenesis of renal tubular. cells

2005

Michelle Southard-Smith discovered genetic modifiers of murine Hirschsprung disease using genome-wide linkage analysis

2005

Matt Breyer and colleagues demonstrate that thiazolidinediones expand body fluid volume through PPAR stimulation of ENaC-mediated renal salt absorption.

2005

Tom Talbot, Tina Hartert, William Schaffner, and Marie Griffin report that asthma is an independent risk factor for invasive pneumococcal disease.

2005

Wes Ely, Gordon Bernard, Robert Dittus and colleagues demonstrate that delirium in a critical determinant of ICU mortality.

2004

Spyros Kalams and colleagues determine that a limited T-cell receptor repertoire on virus-specific cytotoxic T cells is associated with escape from antiviral cytotoxic T lymphocyte responses.

2004

Neil Bhowmick, Eric Neilson, and Hal Moses demonstrate that stromal fibroblasts in interstitial tissues can regulate the oncogenicity of adjacent epithelium.

2003

David Carbone, Piere Maisson, Yu Shyr, Richard Caprioli, and colleagues identify the subset changes in the proteome in small cell lung cancer

2003

William Schaffner and colleagues investigate an outbreak of pseudomonas infections caused by defective bronchoscopes. This results in a global recall of these bronchoscopes.

2002

Jeff Balser, Dan Roden, Mark Anderson, and colleagues identify a calcium sensor in the sodium channel that modulates cardiac excitability.

2002

Dan Roden and colleagues identify genetic factors that predispose to drug-induced cardiac arrhythmia.

2002

Doug Vaughan and colleagues engineer the first transgenic animal model to develop spontaneous coronary arterial thrombosis and myocardial infarction.

2002

Munirathinam Sundaramoorthy and Billy Hudson describe the structure of the NC1 domain from type IV collagen and identify the putative quaternary structures of the Goodpasture antibody binding sites in the NC1 domain of alpha-3 (IV) collagen.

2002

Peggy Kendall and Tom Thomas demonstrate that the natural autoantibody repertoire of nonobese diabetic mice is highly active.

2002

Matt Breyer identifies mechanism of COX-2 selective inhibitors in development or exacerbation of hypertension.

2002

Wonder Drake and colleagues report that a novel mycobacterium is a possible etiologic agent of sarcoidosis based on molecular genetic evidence.

2002

David Johnson and colleagues demonstrate in a randomized study no current regimen was superior to cisplatin and paclitaxel in patients with advanced non-small-cell lung cancer.

2002

Eric Neilson and colleagues demonstrate that tissue fibroblasts derive locally from epithelium through epithelial-mesenchymal transition.

2002

Alfred George repairs a mutant chloride channel using a trans-splicing ribozyme.

2001

Wes Ely, Gordon Bernard, and Robert Dittus develop and validate first method of monitoring delirium in ICU patients, eventually translated into over 8 languages and now implemented by ICUs all over the world as routine ICU management.

2001

Jorge Capdevila reports novel P450 arachidonic acid metabolites are important regulators of blood pressure.

2001

Gordon Bernard, Wes Ely, and colleagues report on the efficacy and safety of recombinant human activated protein C for treatment of patients with severe sepsis for the Prowess Sepsis Study Group.

2001

Doug Kernodle and colleagues demonstrate that the secreted iron-cofactored superoxide dismutase of Mycobacterium tuberculosis inhibits host immune responses and apoptosis, and describe the prototype of a highly effective live-attenuated tuberculosis vaccine based on diminishing microbial immune-inhibitory capacity.

2000

Ray Harris describes the mechanism by which COX-2-derived prostaglandins regulate renal renin expression and secretion.

2000

Robert Coffey and colleagues report on the successful treatment of Menetrier's disease with a monoclonal antibody against the epidermal growth factor receptor.

2000

Mark Anderson and colleagues establish second messenger activation of calcium entry into heart cells by calmodulin kinase II.

2000

Gordon Bernard reports for the ARDS network that a lower tidal volume than used traditionally results in decreased mortality and increases the number of days without ventilator use.

2000

David Robertson, Italo Biaggioni, and colleagues demonstrate that orthostatic intolerance and orthostatic tachycardia in some patients is associated with a norepinephrine-transporter deficiency.

2000

Walter Smalley, Marie Griffin, and Wayne Ray report that FDA-mandated black box warnings on Cisapride do not significantly alter physician prescribing behavior, ultimately eventuating in Cisapride being withdrawn from the market.

2000

Richard D'Aquila and colleagues demonstrate that drug resistant HIV variants remain archived in CD4+ T lymphocytes for years after emergence, even when not detectable in actively replicating virus.

2000

John Newman, John Phillips, Jim Loyd, and colleagues discover the mutation in the bone morphogenic protein type II receptor underlying primary pulmonary hypertension.

2000

Richard Peek and colleagues report that activation of b-catenin in gastric epithelium by carcinogenic Helicobacter pylori contribute to the formation of gastric cancers.

1950-2000

Year

Milestone

1999

Nancy Brown, Jason Morrow, and Jay Gainer demonstrate that bradykinin contributes to the short-term effects of ACE inhibition on blood pressure in normotensive and hypertensive persons.

1999

David Johnson demonstrates that split-dose radiation improves small-cell lung cancer survival in association with cisplatinum.

1998

Raymond Dubois describes the protective effects of cyclooygenase inhibitors on colon cancer.

1997

Steven Hebert clones and identifies the ROMK potassium channel in the kidney.

1996

Steve Davis demonstrates that increased plasma cortisol is the mechanism responsible for antecedent hypoglycemia causing hypoglycemia associated autonomic failure.

1996

Jeffrey Smith and colleagues report the first major susceptibility gene for human prostate cancer.

1995

William Schaffner and Steven Standaert, colleagues describe the ecology and epidemiology of tick-borne Ehrlichiosis.

1995

Mac Linton and Sergio Fazio use bone marrow transplantation to study the effects of macrophages on atherosclerosis.

1995

Alfred George, Dan Roden and colleagues define a molecular defect responsible for sudden death in the congenital long QT syndrome.

1995

Alfred George and colleagues discover that mutations in the human skeletal muscle chloride channel gene cause dominant myotonia congenita.

1994

Raymond Hakim identifies the critical importance of using biocompatible dialysis membranes in the treatment of patients with acute renal failure.

1994

Stephen Raffanti and colleagues start an HIV care program (The Comprehensive Care Center) in Nashville and use an all-electronic medical record as a founding participant in a large multi-center observational cohort study to document outcomes of HIV infection and its treatment.

1993

Martin Blaser and colleagues identify the Helicobacter pylori cytotoxin-associated gene (cagA) as a virulence marker, associated with increased risk for both gastric cancer and peptic ulcer disease.

1993

Oscar Crofford leads 'The Diabetes Control and Complications Trial Research Group' showing the value of tight glucose control with insulin.

1992

Sanford Krantz demonstrates that cytokines produce apoptosis in erythroid progenitors explaining the anemia of chronic disease.

1992

Robert J. Coffey discovered that Menetrier's Disease is caused by overexpression of TNF-alpha, and eight years later that it could be treated with anti-EGF receptor antibody.

1991

Debra Echt reports the landmark Cardiac Arrhythmia Suppression Trial (CAST) showing the pro-arrhythmic effects of encainide and flecainide in patients post-myocardial infarction.

1991

Martin Blaser reports that colonization of the stomach with Helicobacter pylori is strongly associated with an increased risk of gastric carcinoma.

1990

Doug Kernodle and Allen Kaiser demonstrate that in vivo hydrolysis of peri-operative antibiotic prophylaxis by staphylococcal beta-lactamase is a major mechanism leading to deep surgical wound infections.

1990

Jack Roberts and Jason Morrow identify isoprostanes. These and other non-enzymatically-derived lipids are now recognized as markers of oxidant stress and potential mediators of oxidant injury.

1989

Kamal Badr, Ray Harris, Matt Breyer, John Murray, and colleagues provided the first definitive description of the effect of endothelin on the renal microcirculation.

1989

Doug Kernodle describes four kinetic variants of staphylococcal beta-lactamase.

1988

Marie Griffin, Wayne Ray, and William Schaffner provide the first public alert that elderly users of non-steroidal anti-inflammatory drugs were at increased risk for death or serious gastrointestinal toxicity.

1987

Billy Hudson reports the NC1 domain of the alpha-3 (IV) collagen chain is the target antigen of Goodpasture's disease.

1986

Garret FitzGerald and John Oates define the molecular basis for the efficacy of low dose aspirin to prevent acute coronary events via selective inhibition of platelet thromboxane production.

1985

William Stone identifies beta-2 microglobulin in dialysis-related amyloid.

1982

William Stone and colleagues first describes the failure of antibodies in Goodpasture's disease to stain kidney tissue in Alport's syndrome, providing the first biochemical link between the two diseases.

1981

Rose Robertson, John Oates, and colleagues describe the relationship between thromboxane A2 and coronary vasospasm.

1981

Hal Moses describes a transforming growth factor in chemically-modified cell lines and helps to open the field of TGF-beta biology.

1978

Dan Roden, Ray Woosley, Grant Wilkinson, and Alastair Wood identify instances of genetically-determined drug metabolism and effect, laying the groundwork for the field of pharmacogenetics.

1978

Lloyd King, Graham Carpenter, and Stanley Cohen discover that epidermal growth factor stimulates receptor autophosphorylation.

1976

Alastair Wood and Bob Vestal identify age as a key factor modulating heart rate response to catecholamines.

1976

Zell McGee and colleagues define species-specific factors that allow Neisseria (gonoccoci and meningococci) to bind to epithelial cells.

1975

John Oates and colleagues report the overproduction of prostaglandins in lung cancer, providing the first evidence that the inducible cyclooxygenase may play a role in certain malignancies.

1975

Grant Wilkinson and David Shand describe first-pass metabolism, a common feature for the processing of many drugs.

1974

Kenneth Brigham demonstrates that gram-negative bacteremia can cause increased lung permeability and acute respiratory distress syndrome.

1972

William Schaffner, Marian Ann Melly, and Glenn Koenig perform ground-breaking investigations tracing sepsis in hospitalized patients to contaminated IV fluids.

1972

Roger Des Prez and Robert Goodwin provide the first comprehensive description of mediastinal fibrosis from infection with histoplasmosis.

1971

Glenn Koenig and Jay S. Goodman describe the immunologic detection of cryptococcal antigen for diagnosis of cryptococcal meningitis.

1968

Anderson Spickard, Glenn Koenig, David Rogers and colleagues develop a regimen for using amphotericin B to treat histoplasmosis and other disseminated fungal infections.

1967

Sanford Krantz describes the immune basis for pure red cell aplasia and later shows it response to immunosuppressive therapy.

1966

Robert Hartmann describes the "sugar-water" test for paroxysmal nocturnal hemoglobinuria..

1963

William Coppage and Grant Liddle describe a familial renal tubular disorder simulating primary aldosteronism, later known as Liddle's syndrome (pseudohyperaldosteronism) that is now recognized by a mutation in the apical sodium channel along the cortical collecting duct.

1963

Sanford Krantz describes the effect of erythropoietin on hemoglobin synthesis by marrow cells and later describes its kinetic binding to a putative erythropoietin receptor.

1963

Elliot Newman established one of the first General Clinical Research Centers at Vanderbilt and his notion of how it should operate became a model across the country.

1962

Clifton Meador and Grant Liddle report the ectopic production of ACTH from a tumor producing Cushing's syndrome.

1960

David Rogers, Marian Ann Melly, and M. Glenn Koenig publish landmark findings showing differences in phagocytosis and intracellular survival of pathogenic versus non-pathogenic staphylocci.

1960

Grant Liddle demonstrates that Cushing's disease is primarily a pituitary disorder with increased levels of ACTH at any level of plasma cortisol..

1960

Grant Liddle develops the dexamethesone suppression test to assess the pituitary-adrenal axis. Later Liddle and Clifton Meador show this is due to suppression of ACTH.

1960

John Oates describes one of the early, important anti-hypertensive drugs that became alpha-methyldopa (Aldomet).

1959

Alexander Townes and Grant Liddle develop the metyrapone stimulation test to assess pituitary reserve

1958

David E. Rogers first reports that pneumonia from influenza by itself could be fatal.

1957

Grant Liddle describes the inhibitory effects of spironolactone on aldosterone expression.

1954

Elliot Newman reports the changes in solute excretion following alteration of posture and position.

1953

Paul Teschan first delivers hemodialysis to patients in a war zone.

1953

William Darby demonstrates salt excess as a basis for acquired hypertension.

Pre 1950

Year

Milestone

1943

Rudoph Kampmeier the leading authority on syphilis publishes his classic textbook Essentials of Syphilology.

1939

Samuel Riven, Hugh Morgan, and Alfred Blalock report the first cure of myasthenia gravis by removal of a thymoma.

1938

William Darby first describes protein M (folate) deficiency anemia. Later he went on to identify a number of other vitamin deficiency states and helped establish the minimal daily requirements for iron and vitamins in pregnancy.

1935

Tinsley Harrison after a decade of fundamental research publishes his classic textbook entitled The Failure of the Circulation. Fifteen years later he published his now famous textbook Principles of Internal Medicine.

1933

John Youmans provides the first comprehensive description of the causes of endemic nutritional edema.

1933

John Youmans reports the first formula for estimating osmotic pressure from measurements of albumin and total protein in human blood.

1927

Sidney Burwell measures the physiologic effects of digitalis on cardiac output.

1926

Tinsley Harrison and Alfred Blalock describe the effect of oxygen deficiency on cardiac output.

1924

Tinsley Harrison and William Dock report the effects of arteriovenous fistulas on cardiac output.

1924

Hugh Morgan measures the changes in blood count and blood gases in patients with pneumonia.

1924

Canby Robinson and Sidney Burwell describe methods for measuring PO2 and PCO2 in mixed venous blood